Definition
Non-union
- arrest of progression to union at fracture site
- > 6-9 /12
- no visible progressive signs of healing for at least three consecutive months
- individualise for each fracture
- when the surgeon believes the fracture has little or no chance to heal
Delayed union
- failure of fracture to unite within expected time
- still may spontaneously unite
Fracture Healing
Phases
- haematoma / inflammation / neoangiogenesis
- soft callus
- hard callus
- remodelling
Haematoma
- immediate at site of injury
Inflammation
- vasodilation & exudation of plasma & leucocytes
- polymorphs, histiocytes, & mast cells appear
- process of removing debris begins
Neoangiogenesis
- rapid development of an extra-osseous blood supply
- derived from surrounding soft tissue
- invasion of fibrovascular tissue that replaces the haematoma
- lays down collagen & matrix that later becomes mineralised to form woven bone (provisional/ primary/ soft callus)
Soft callus
- primary callus response within days / weeks
- inner cambrial layer (as opposed to outer fibrous layer) of periosteum
- surrounding soft issue fibroblasts
- forms fibrocartilage matrix
Hard callus
- external bridging callus within weeks
- woven bone formed by mineralisation of fibrocartilage matrix
- arises most probably from osteoinduction of cells which do not have direct connection with bone
- blood supply reliant on surrounding soft tissue
- primary purpose is to arrest movement between bone fragments
- strong evidence it arises from by bioelectric feedback (piezoelectric effect)
Remodelling
Bone remodelling in response to local stress / strain in accordance to Wolff's Law
Bone Healing
Primary Bone Healing
Anatomical reduction and absolute fixation
- no gap, no strain
- no callous is form
- intramembranous ossification (osteoid onto CT membrane)
Creeping substitution
- advancing front of osteoclasts
- osteoclasts form cutting cones across cortical bone allowing revascularisation
- followed by osteoblasts laying down bone matrix
- endosteal callous is formed
Secondary Bone healing
Normal phases of bone healing
- endochondral ossification
- mineralisation of fibrocartilaginous matrix
- soft and hard callous
Mechanobiology of Skeletal Regeneration
Differentiation of mesenchymal tissue into bone, cartilage or fibrous tissue
A. Intramembranous ossification
- in areas of low stress / strain
- mesenchymal stem cells
- no cartilage stage
- osteoid secreted onto CT
- woven bone
- eventually becomes lamellar bone
B. Endochondral ossification
- low to moderate tensile strain & hydrostatic tensile stress
- chondrocytes make cartilage
- osteoprogenitor cells become osteoblasts and secrete osteoid onto calcified cartilage matrix
C. Chondrogenesis
- if hydrostatic compressive stress or poor vascularity
D. Fibrous tissue
- if high tensile strain
E. Fibrocartilage
- if tensile strain with hydrostatic compressive stress
Concept Interfragmentary Strain
Different tissue can tolerate different amounts of strain
- Fibrous ~ 100% strain
- Chondroid ~ 20% strain
- Bone < 2% strain
Interfragmentary strain (motion) is inversely proportional to the fracture gap
- small gap with small motion --> large strain
- large gap with small motion --> small strain
Bone resorption may decrease strain & hence allow granulation tissue to form
- then the callus will stabilize the fracture enough to allow the next stage to progress
- hence amount callus proportional to stability
Aetiological factors
Patient factors
Injury
Treatment
Patient factors
Age
Activity
Immoderate, noncompliant patient
Nutrition / catabolic states
Anaemia
Smoking
- decreases peripheral O2 tension
- dampens peripheral blood flow
Alcohol
DM
Peripheral Neuropathy
Immunocomprimise
Osteomalacia
- failure to mineralise callous
- correct abnormality
Pharmacological agents
- Steroids
- Cytotoxics
- Ciproflaxacin
- NSAIDS
- Irradiation
Giannoidin et al JBJSB 2000
- 32 unions and 67 non-unions
- NSAID use significant
- delayed healing in united group also
Injury
Open fracture
Significant soft tissue trauma
Soft tissue interposition
Infection
- inflammatory response
- disrupts callous, increases fracture gap and motion
Pathological fracture
Malignant tissue
Osteoporosis
Anatomic Location
- Poor vascularity / NOF / scaphoid / 5th MT
Intact fellow bone
Excessive bone loss
Segmental injury
Comminution
Displacement
- shown to be important in the tibia
Synovial fluid / Intra-articular
Treatment
Distraction of fracture
Inadequate stability with excessive movement
Extensive approach with vascular compromise
No axial load
Classification Non-union
1. Hypertrophic
- elephant foot (abundant callous)
- horse hoof (less abundant callous)
- adequate vascularity, poor mechanical environment for healing
- predominantly fibrocartilage in gap
- inadequate stabilization / excessive strain
- 92-95% non-infected non-unions tibia & fibula
2. Oligotrophic
- no callous on x-ray
- vascularity on bone scan
3. Atrophic / avascular
- pencilling of bone ends
- avascular
- no vascularity on bone scan
- fibrous or cartilage interposition
- needs osteoinduction + stabilization
- debride non-union / rigid fixation / compress / bone graft
4. Pseudarthrosis
- non-union with fluid-filled cavity
- synovial-like membrane & pseudocapsule formation
- new joint at fracture site
- usually painless motion
- needs excision of pseudoarthrosis / rigid fixation / compression / bone graft
Management
Options
1. Rigid stabilization
2. Autograft / allograft
3. Other modalities
- Electrical stimulation
- US therapy
- BMP
- Bone marrow aspirate
Electrical Stimulation
Science
Based on principle that bone healing primarily occurs as a result of strain-generated electrical potentials
- no effect on fully fibrous non-union
- must have some biological process occurring
Three types
1. DC
- negative pole (cathode) has to be implanted into fracture site
- produces sustained injury potential that increases inflammatory respons
- invasive / risk infection
2. AC
- use conductive medium
- paste electrode either side of affected extremity
- only work on soft & hard callus
- increase cAMP, collagen synthesis & calcification during soft & hard callus stages of healing
3. Pulsed Electromagnetic Fields
- most used clinically
- placed externally without need for inductive media
- electrodes either side of non-union in cast or brace (no need to contact skin)
- can be symmetrical or asymmetrical pulse
- help convert soft to hard callus
Results
Simonis et al Injury 2003
- RCT of electrical stimulation v placebo in tibial non union
- increased union rate in smokers from 67% to 100%
Sharrard JBJS Br
- RCT of 45 tibial delayed union
- significantly improved union rate c.f. control
Pulsed US
Science
Ultrasound is acoustic radiation at frequency above human hearing
- mechanical energy that can be transmitted into the body as high-frequency pressure waves
- micromechanical strains may promote bone formation in same manner as postulated by Wolff's Law
Exact mechanism unknown but may be
- enhanced production of osteoinductive agents
- direct stimulatory effect on osteoblasts
- increased blood supply
Results
Exogen Registry
- 1700 delayed unions 91% healing rate
- 700 non-unions 85% healing rate
Heckman JBJS 1994
- prospective, double-blind, randomised, placebo-controlled trial
- closed or grade 1 open tibial diaphyseal fractures
- all US patients healed (average 96 days) vs some nonunions in placebo group (average 150 days)
- healing times reduced in smokers
BMP
Science
See Miscellaneous / Bone graft
Results
Friedlaender et al JBJS Am 2001
- as efficacious as autograft in established tibial non union
Govender et al JBJS Am 2002
- RCT of control v BMP in open tibial fractures
– less secondary interventions, accelerated time to union, reduced infection rates
Jones et al JBJS Am 2006
- RCT allograft + BMP2 v autograft in tibial diaphyseal cortical defects
- similar rates of healing, reduced blood loss in BMP group
Garrison et al Cochrance Database Review 2010
- limited evidence for BMP in acute fracture
- unclear evidence in non union
- likely economically viable in severe open tibial fractures
Bone Marrow Aspirate
Results
Hernigou et al JBJS Am 2006
- 20mls BMA injected percutaneously into 60 atrophic tibial non unions
- union obtained in 53 cases